Synergistic developmental toxicity of polycyclic aromatic hydrocarbons: Towards a mechanistic understanding

Richard Di Giulio, Sonya Billiard, Joel Meyer, Deena Wassenberg, Peter Hodson

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PAH invariably occur in the environment as complex mixtures of non-substituted PAH, alkyl-PAH, and N-, S-, and O-ring substituted PAH. Recent studies with mixtures derived from pollution events in marine and estuarine systems, e.g., the Exxon Valdez oil spill in Alaska and a wood treatment facility in the Elizabeth River, VA, revealed potent developmental toxicities in fish embryos; most pronounced were cardiovascular defects. These dioxin-mediated effects are associated with the binding of dioxin to the aryl hydrocarbon receptor (AHR), although mechanisms downstream of receptor binding remain unresolved. Other experiments examined interactions between AHR agonists (BaP and β-napthoflavone) and CYP1A inhibitors (α-napthoflavone, piperonyl butoxide, fluoranthene, carbazole and dibenzothiophene); these revealed pronounced synergistic developmental toxicities between AHR agonists and CYP1A inhibitors. This contrasts with the protective effect reported for CYP1A inhibition on the developmental toxicity of dioxins. Current work with zebrafish embryos employing morpholinos to block translation of AHR2 and CYP1A mRNA are consistent with the chemical inducer/inhibitor studies. This observed synergy has important implications for accepted additive models of PAH toxicity, as systems contaminated by PAH contain both AHR agonists and CYP inhibitors. This is an abstract of a paper presented at the symposium on "Pollutant Responses in Marine Organisms" (Alessandria, Italy 6/19-23/2005).

Original languageEnglish (US)
Pages (from-to)S45-S46
JournalMarine Environmental Research
Issue numberSUPPL. 1
StatePublished - 2006
Externally publishedYes

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